Réaction #43694

Équation de réaction

methyl iodide

HCl

title compound

4-(7-Benzyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile

4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile

LHMDS

→

4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride

Solvants

diethyl ether

acetone

THF

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGthe solution is stirred for 15 min
2. 2
   AutreThe reaction mixture is quenched by addition of NH4Cl
3. 3
   Extractionextracted with EtOAc
4. 4
   LavageThe organic solution is washed with brine
5. 5
   Séchagedried (anhydrous sodium sulfate)
6. 6
   Autreevaporated to an oil
7. 7
   AutrePurification by flash chromatography (silica gel)
8. 8
   Lavageeluting with EtOAc:MeOH:NH4OH (95:5:0.5)
9. 9
   Autregives the free base which

Mode opératoire

To a solution of the title compound of Example 3, 4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile (0.24 g, 0.63 mmol) in 5 mL of THF at −78° C. is added LHMDS (0.70 mL, 0.70 mmol) and the resulting solution is stirred for 15 min. To this solution is added methyl iodide (0.040 mL, 0.67 mmol) and the solution is stirred for 15 min, then warmed gradually to RT. The reaction mixture is quenched by addition of NH4Cl and extracted with EtOAc. The organic solution is washed with brine, dried (anhydrous sodium sulfate) and evaporated to an oil. Purification by flash chromatography (silica gel) eluting with EtOAc:MeOH:NH4OH (95:5:0.5) gives the free base which is dissolved in acetone and HCl (g) in diethyl ether is added to afford 4-(7-benzyl-5-methyl-6-oxo-5,6,7,8-tetrahydro-imidazo[1,5-a]pyrazin-5-yl)-benzonitrile hydrochloride: m.p. 230-232° C.; 1H-NMR (DMSO-d6) δ 9.54 (1H, s), 7.90 (2H, d, J=8.7), 7.74 (1H, s), 7.32 (3H, m), 7.22 (2H, d, J=8.7), 7.15 (2H, m), 4.73 (1H, d, J=16.9), 4.71 (1H, d, J=14.6), 4.66 (1H, d, J=14.6), 4.12 (1H, d, J=16.9), 2.25 (3H, s); 13C-NMR (DMSO-d6) δ 163.1, 141.1, 133.8, 132.3, 131.3, 126.8, 125.8, 125.7, 124.0, 123.7, 116.2, 114.2, 110.0, 64.6, 48.4, 38.5, 22.6; e/z (ES) 343 (M+1, 100%); calculated for C21H18N4O HCl, C, 66.58; H, 5.05; N, 14.79. found C, 66.41; H, 5.01; N, 14.80.

Source